Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation. (August 2000)

• Record Type: Journal Article
• Authors: Stallcup, M. R.; Chen, D.; Koh, S. S.; Ma, H.; Lee, Y.-H.; Li, H.; Schurter, B. T.; Aswad, D. W.
• Is Part Of: Biochemical Society transactions. Volume 28:Number 4(2000)
• Page Start: 415
• Page End: 418
• Publication Date: 2000-08
• Subjects: co-activator -- nuclear receptors, protein acetylation -- protein methylation -- steroid receptor; AD, activation domain -- CARMI, co-activator-associated arginine methyltransferase I -- CBP, CREB-binding protein -- NR, nuclear hormone receptor -- PRMTI, protein arginine methyltransferase I; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0280415
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Nuclear hormone receptors (NRs) activate transcription by binding to specific enhancer elements associated with target genes. Transcriptional activation is accomplished with the help of complexes of co-activator proteins that bind to NRs. p160 co-activators, a family of three related 160 kDa proteins, serve as primary co-activators by binding directly to NRs and recruiting additional secondary co-activators. Some of these (CBP/p300 and p/CAF) can acetylate histones and other proteins in the transcription complex, thus helping to modify chromatin structure and form an active transcription initiation complex. We recently discovered co-activator-associated arginine methyltransferase 1 (CARM1), which binds to p160 co-activators and thereby enhances transcriptional activation by NRs on transiently transfected reporter genes. CARM1 also methylates specific arginine residues in the N-terminal tail of histone H3 in vitro. A related arginine-specific protein methyltransferase, PRMT1, also binds p160 co-activators and enhances NR function. PRMT1 methylates histone H4 in vitro. The enhancement of NR function by CARM1, PRMT1 and p300 depends on their interactions with p160 co-activators. In the presence of p160 co-activators, some pairs of these three secondary co-activators provide a highly synergistic enhancement of NR function on transiently transfected reporter genes. We have also observed an enhancement of NR function on stably integrated reporter genes by these co-activators. We propose that the synergy of co-activator function between p300, CARM1 and PRMT1 is due to their different but complementary protein modification activities.